During our previous funding period we showed that a clinical dose of shock waves applied to the lower pole calyx of one kidney induces a predictable lesion at F2, reduces renal blood flow in both kidneys, and produces a renal response the severity of which is related to risk factors. These risk factors include kilovoltage, kidney size, number of shock waves administered, pre-existing renal inflammation or disease, and shock waves applied to both poles of the same kidney during the same treatment session. Since the newer 3rd-generation lithotripters are known to be less effective at breaking stones and appear to be more prone to cause adverse effects than the Dornier HM3 lithotripter, this renewal application will expand our existing focus to include studies of the new and emerging lithotripters. The goal of such studies is to develop new treatment strategies and technologies with the potential to improve the efficacy and safety of all lithotripters. In Aim 1, Project 1 will determine the time-course and mechanism of SWL-induced renal vasoconstriction. We will interact with Project 3 for this Aim. Aim 2 will focus on several new risk factors for SWL. These factors include conditions that might be expected to worsen or lessen the tendency for bleeding to occur in renal tissue damaged by shock waves (e.g., high or low blood pressure) and parameters for administration of SWs (e.g., pulse repetition rate). We will interact with Project 2 for this Aim. Aim 3 will correlate cavitation with the vascular lesions to determine if cavitation is the primary mechanism of cell injury. We will interact with Projects 3 & 4 for this Aim. Aim 4 will characterize the mechanism whereby pretreatment with low-energy shock waves protects the kidney form vascular damage induced by high-energy shock waves. It is conceivable that most of the cellular damage induced by a clinical dose of shock wave can be prevented by our pretreatment protocol, thereby, reducing any long-term renal complications for the patient, especially those receiving multiple treatments. We will interact with Project 2 for this Aim. Aim 5 will assess a 3rd generation lithotripter (e.g., Compact Delta that has a tight-focal-zone and high-incident-pressure) and an emerging technology in SWL (twin head lithotripter, the Direx "Duet") for their potential to cause renal trauma and impair renal function. We will interact with Projects 2 and 3 for this Aim. All of these proposed studies aim at understanding the adverse effects of SWs and advancing the safety of SWL for all stone patients at a time when reports of adverse effects in SWL are on the rise.